title: A double diastereoselective Michael-type addition as an entry to conformationally restricted tn antigen mimics.
abstract: A totally stereocontrolled C-Michael addition of serine-equivalent C-nucleophiles to tri-O-benzyl-2-nitro-d-galactal was used as the key step to synthesize several pyrano[3,2-b]pyrrole structures. These scaffolds could be regarded as conformationally restricted Tn antigen mimics, as we have demonstrated by biological assays. The pyranose rings retain their (4)C1 chair conformation, as shown by molecular modeling and NMR spectroscopy. The expected bioactivity was established by a competition-tailored enzyme-linked lectin assay using both soybean and Vicia villosa agglutinins as model lectins. The facile described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational features and bioactivity demonstrate the prepared glycomimics to be promising candidates for further exploitation of this scaffold to give glycans for lectin blocking and vaccination.
authors.affiliation: Departamento de Química and Centro de Investigación en Síntesis Química, Universidad de La Rioja , 26006 Logroño, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Aydillo
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Navo
authors.forename: Jesús H
authors.initials: JH
authors.lastname: Busto
authors.forename: Francisco
authors.initials: F
authors.lastname: Corzana
authors.forename: María M
authors.initials: MM
authors.lastname: Zurbano
authors.forename: Alberto
authors.initials: A
authors.lastname: Avenoza
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Peregrina
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology; D015195:Drug Design; D006020:Glycopeptides / Q000737:chemistry*; D037102:Lectins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D037121:Plant Lectins / Q000138:chemical synthesis* / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D006020:Glycopeptides; D037102:Lectins; D037121:Plant Lectins; D011134:Polysaccharides; C040286:Tn antigen; C042242:Vicia lectins